Studies by us and others have shown that delayed hypersensitivity challenge reactions at sites of malignant tumors result in regression of a spectrum of tumors in man and animals. A central finding of these studies appears to be the relationship of the anti-tumor effects of the delayed hypersensitivity reaction to the non-cellular and cellular components, particularly macrophages, of the cell mediated immune system. Our preliminary observations indicate that local administration of the non-cellular mediators of the delayed hypersensitivity reaction (i.e. lymphokines) produce reactions resembling delayed hypersensitivity responses and can result in regression of tumors in man. One of the prime aims of the proposed investigations is to determine the validity of these preliminary findings and their relation to the integrity of the immune system. Material with lymphokine activity (MLA) and control material will be obtained from primary cultures of normal human lymphocytes. The effects of MLA administration to accessible tumors of patients with advanced cancer will be correlated with their immunocompetence. Concurrent studies will be carried out on the in vitro response of lymphocytes of these patients to stimulation with lymphokines. The effects of serum of advanced cancer patients on the capacity of normal lymphocytes to produce lymphokines will also be investigated. The data will be evaluated with respect to possible interrelations between effects of MLA on tumors, skin test responses to MLA, parameters of immunocompetence, serum inhibitors of lymphocyte responses and functional defects in lymphocytes of cancer patients. The duration of regression of malignant lesions induced by MLA and the possible relationship between skin test response to MLA and the overall clinical course will also be explored. The proposed investigations have bearing upon central questions pertaining to host defense mechanisms against neoplastic cells. As such, they have practical as well as theoretical implications.